With the on-going uptrend in age distribution of the population, a variety of brain function improving agents have been proposed.
Nerve growth factor (NGF) has been considered to be a nutrient factor essential to the maintenance of the living body, which serves to promote differentiation of the sympathetic and sensory nerve cells and brain nerve cells in the stage of genesis. The characteristics of NGF as a chemical compound (protein) have also been elucidated [Nature, 302, 538, (1983)].
In patients bearing senile dementia or Alzheimer's disease, the biosynthesis and secretion of NGF are either at a low level or defected. Therefore, attempts have been made to use NGF for the treatment of maladies in degenerative nervous system disorders such as senile dementia and Alzheimer's disease [Nature, 329, 65, (1987)]. However, since the levels of biosynthesis and secretion of NGF are generally low, it is very difficult to isolate NGF from the living tissue or produce it by cloning in amounts useful for therapeutic and other purposes. On the other hand, it is known that NGF is synthesized in vivo in the sympathetic and sensory nerve cells and brain nerve cells [Biochemical Biophysical Research Communications, 136, 57, (1986)].
Under the circumstances, attempts have been made to stimulate the secretion of NGF in various nerve cells and cerebral neurons by means of catechol compounds [The Pharmaceuticals Monthly (Japan), 29, 49, (1987)]. However, these compounds are not satisfactory in the degree of activity or on the aspect of cytotoxicity.
From the above points of view, the inventors have made extensive research into developing an NGF secretion inducing agent that may take the place of cathecol compounds and have found that certain aromatic amide compounds have unexpectedly potent NGF secretion inducing activity.